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A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model
Hu,Mi; Varier,Krishnapriya M.; Li,Zhicao; Qin,Xujie; Rao,Qing; Song,Jingrui; Hu,Anling; Hang,Yubing; Yuan,Chunmao; Gajendran,Babu; Shu,Liping; Wen,Min; Li,Yanmei; Liu,Haiyang
2021
发表期刊BIOMEDICINE & PHARMACOTHERAPY
ISSN0753-3322
卷号141页码:111877
摘要Leukemia is responsible for a reason of death, globally. Even though there are several treatment regimens available in the clinics against this disease, a perfect chemotherapeutic agent for the same is still under investigation. Natural plant-derived secondary metabolites are used in clinics to treat leukemia for better benefits with reduced side-effects. Likely, several bioactive compounds from Callistemon sp. were reported for their bioactive benefits. Furthermore, acylphloroglucinol derivatives from Callistemon salignus, showed both antimicrobial and cytotoxic activities in various adherent human cancer cell lines. Thus, in the present study, a natural acylphloroglucinol (2,6-dihydroxy-4-methoxyisobutyrophenone, L72) was tested for its antiproliferative efficacy in HEL cells. The MTT and the cell cycle analysis study revealed that L72 treatment can offer antiproliferative effects, both time and dose-dependent manner, causing G2/M cell cycle arrest. The western blot analysis revealed that L72 treatment triggered intrinsic apoptotic machinery and activated p21. Likewise, L72 could downregulate the gene expressions of XIAP, FLT3, IDH2, and SOD2, which was demonstrated by qPCR analysis, thus promoting its antiproliferative action. The L72 could impede STAT3 expression, which was evidenced by insilico autodock analysis and western blot analysis using STAT3 inhibitor, Pimozide. The treatment of transgenic (Flk-1+/egfr+) zebrafish embryos resulted in the STAT3 gene inhibition, proving its anti-angiogenic effect, as well. Thus, the study revealed that L72 could act as an antiproliferative agent, by triggering caspase-dependent intrinsic apoptosis, reducing cell proliferation by attenuating STAT3, and activating an anti-angiogenic pathway via Flk1-inhibition.
关键词Acylphloroglucinol HEL cells Intrinsic apoptotic pathway Anti-angiogenesis STAT3 Flk-1 CALLISTEMON-CITRINUS TUMOR ANGIOGENESIS DNA DERIVATIVES ANTICANCER APOPTOSIS ACTIVATION INHIBITORS TARGETS LEAVES
DOI10.1016/j.biopha.2021.111877
WOS记录号WOS:000693333500001
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/73693
专题中国科学院昆明植物研究所
作者单位1.Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Dept Immunol, Guiyang 550014, Peoples R China
2.Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550014, Peoples R China
3.Chinese Acad Sci, Guiyang 550014, Peoples R China
4.Guizhou Med Univ, Key Lab Regenerat Med Guizhou Prov, Guiyang 550004, Guizhou, Peoples R China
5.Guizhou Med Univ, Sch Pharmaceut Sci, Guiyang 550025, Guizhou, Peoples R China
6.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Yunnan, Peoples R China
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Hu,Mi,Varier,Krishnapriya M.,Li,Zhicao,et al. A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model[J]. BIOMEDICINE & PHARMACOTHERAPY,2021,141:111877.
APA Hu,Mi.,Varier,Krishnapriya M..,Li,Zhicao.,Qin,Xujie.,Rao,Qing.,...&Liu,Haiyang.(2021).A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model.BIOMEDICINE & PHARMACOTHERAPY,141,111877.
MLA Hu,Mi,et al."A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model".BIOMEDICINE & PHARMACOTHERAPY 141(2021):111877.
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